This application is for a continuation of the NIMH-CRB Psychobiology Depression Program (Bio), which is a collaborative undertaking between five research centers aimed at defining changes in biogenic amine metabolism (norepinephrine and serotonin), adrenocortical function, growth hormone response to insulin-induced hypoglycemia, erythrocyte cation concentration, and cerebrospinal fluid cyclic AMP concentration in carefully defined groups of bipolar (depressed and manic) and unipolar depressed patients as compared with several control groups. As part of the program, patients participate in a double-blind treatment protocol involving the administration of either imipramine or amitriptyline during which plasma and cerebrospinal fluid concentration of both tertiary and secondary tricyclic compounds are obtained. During the coming year, we will continue studying patients and control subjects, assaying appropriate samples in our laboratories, as well as submitting samples obtained from our patients to collaborating centers.